Table 8.
Summary of clinical outcomes of first-line key trials
| SHARP790 |
REFLECT796 |
IMbrave150797,831 |
HIMALAYA828 |
||||||
|---|---|---|---|---|---|---|---|---|---|
| SOR | PBO | LEN | SOR | ATZ/BEV | SOR | DURV/TREM | DURV | SOR | |
| Number of patients allocated | 299 | 303 | 478 | 476 | 336 | 165 | 393 | 389 | 389 |
| Median OS (months) | 10.7 | 7.9 | 13.6 | 12.3 | NR (19.2)† | 13.2 (13.4)† | 16.4 | 16.6 | 13.8 |
| HR (95% CI) | 0.69 (0.55–0.87); P<0.001 | 0.92 (0.79–1.06) | 0.58 (0.42–0.79); P<0.001 | 0.78 (0.65–0.92) for D/T vs. SOR | |||||
| 0.86 (0.73–1.03) for D vs. SOR | |||||||||
| Median PFS (months) | NA | NA | 7.4 | 3.7 | 6.8 | 4.3 | 3.78 | 3.65 | 4.07 |
| HR (95% CI) | NA | 0.66 (0.57–0.77); P<0.0001 | 0.59 (0.47–0.76); P<0.001 | 0.90 (0.77–1.05) for D/T vs. SOR | |||||
| 1.02 (0.88–1.19) for D vs. SOR | |||||||||
| Median TTP (months) | 5.5 | 2.8 | 8.9 | 3.7 | NA | NA | 5.42 | 3.75 | 5.55 |
| HR (95% CI) | 0.58 (0.45–0.74); P<0.001 | 0.63 (0.53–0.73); P<0.0001 | NA | NA | |||||
| ORR/CR (%) | 2.0/0.0 | 1.0/0.0 | 24.1/1 | 9.2/<1 | 27.3/5.5 | 11.9/0.0 | 20.1/3.1 | 17.0/1.5 | 5.1/0.0 |
| DCR (%) | 43 (73*) | 32 (68*) | 75.5 | 60.5 | 73.6 | 55.3 | 60.1 | 54.8 | 60.7 |
| Median duration of treatment (months) | 5.3 | 4.3 | 5.7 | 3.7 | 7.4 for A | 2.8 | NA | NA | NA |
| 6.9 for B | |||||||||
| Median duration of response (months) | NA | NA | NA | NA | (18.1)† | (14.9)† | 22.34 | 16.82 | 18.43 |
| Response evaluation | RECIST v1.1 | mRECIST | RECIST v1.1 | RECIST v1.1 | |||||
SHARP, A Phase III Study of Sorafenib in Patients With Advanced Hepatocellular Carcinoma; REFLECT, A phase III, multinational, randomized, noninferiority trial compared the efficacy and safety of lenvatinib (LEN) and sorafenib for the treatment of unresectable hepatocellular carcinoma; HIMALAYA, Study of Durvalumab and Tremelimumab as First-line Treatment in Patients With Advanced Hepatocellular Carcinoma; SOR, sorafenib; PBO, placebo; LEN, lenvatinib; ATZ, atezolizumab; BEV, bevacizumab; DURV, durvalumab; TREM, tremelimumab; OS, overall survival; NR, not reached; HR, hazard ratio; CI, confidence interval; D, durvalumab; T, tremelimumab; PFS, progression-free survival; NA, not available; TTP, time-to-progression; ORR, objective response rate; CR, complete response; DCR, disease control rate; A, atezolizumab; B, bevacizumab; RECIST v1.1, Response Evaluation Criteria in Solid Tumors version 1.1; mRECIST, modified Response Evaluation Criteria in Solid Tumors.
In the SHARP trial, the disease-control rate was presented as the percentage of patients who had a best-response rating of complete or partial response or stable disease that was maintained for at least 28 days after the first demonstration of that rating on independent radiologic review. Numbers in parenthesis indicate the percentage of patients showing complete or partial response or stable disease by independent radiologic review.
Updated analysis of IMbrave150 trial was performed 12 months after the primary analysis and presented.